A novel aminophospholipid transporter exclusively expressed in spermatozoa is required for membrane lipid asymmetry and normal fertilization.
A novel aminophospholipid transporter exclusively expressed in spermatozoa is required for membrane lipid asymmetry and normal fertilization.
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DOI：
10.1016/j.ydbio.2003.11.004
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发表时间：
2004-03
影响因子：
2.7
通讯作者：
Lei Wang;Crystal Beserra;D. Garbers
中科院分区：
文献类型：
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作者：
Lei Wang;Crystal Beserra;D. Garbers
通过使用功能无偏的信号肽陷阱筛选，我们发现了一种atp依赖的氨基磷脂转运蛋白，该转运蛋白仅在精子顶体区域表达；它与翻转酶FIC1相似度约为62%。我们破坏了转运基因，发现雄性无鼠的产仔体积略小于野生型雄性。精子形态和活力与野生型幼崽相同，但测定外膜小叶磷脂或磷脂酰丝氨酸（PS）含量的方法（merocyanine和annexin）表明，PS在精子获能之前就已经存在于空精子的外小叶中。在无透明带的卵子中加入无精子时，受精率正常，但在细胞外基质存在的情况下，与透明带紧密结合或穿透透明带的转运体/ -精子较少，发生顶体反应的精子较少。体外受精受到损害，特别是在早期时间点或在无精子和卵子混合后精子浓度低的情况下。因此，一种新的仅在精子中表达的氨基磷脂转运蛋白对于磷脂在双分子层中的正常分布以及透明带的正常结合、渗透和信号传导至关重要。
Through the use of a functionally unbiased signal peptide trap screen, we have discovered an ATP-dependent aminophospholipid transporter that is exclusively expressed in the acrosomal region of spermatozoa; it is about 62% similar to the flippase, FIC1. We disrupted the transporter gene and found that the size of litters from male null mice was slightly smaller than found with wild-type males. Sperm morphology and motility were the same between null and wild-type littermates, but agents (merocyanine and annexin) that measure phospholipid packing or phosphatidylserine (PS) in the outer membrane leaflet showed that PS already existed in the outer leaflet of null spermatozoa before sperm capacitation. Fertilization rates were normal when null spermatozoa were added to zona pellucida-free eggs, but in the presence of the extracellular matrix, fewer transporter−/−spermatozoa bound tightly or penetrated the zona pellucida (ZP), and fewer underwent acrosome reactions. In vitro fertilization was compromised, especially at early time points or at low sperm concentrations after mixing null spermatozoa and eggs. Thus, a new aminophospholipid transporter expressed exclusively in spermatozoa is critical for normal phospholipid distribution in the bilayer, and for normal binding, penetration, and signaling by the zona pellucida.